WEE2

Summary

WEE2 (WEE2 oocyte meiosis inhibiting kinase, HGNC:19684) is a protein-coding gene on chromosome 7q34, encoding Wee1-like protein kinase 2 (P0C1S8). Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits CDK1/CDC2 and acts as a key regulator of meiosis during both prophase I and metaphase II.

Predicted to enable protein tyrosine kinase activity. Predicted to be involved in several processes, including female pronucleus assembly; negative regulation of cyclin-dependent protein serine/threonine kinase activity; and regulation of meiotic cell cycle. Located in cytosol; nucleoplasm; and plasma membrane.

Source: NCBI Gene 494551 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oocyte maturation defect 5 (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 113 total — 7 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001105558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19684
Approved symbol	WEE2
Name	WEE2 oocyte meiosis inhibiting kinase
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16107, WEE1B
Ensembl gene	ENSG00000214102
Ensembl biotype	protein_coding
OMIM	614084
Entrez	494551

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000397541, ENST00000493845, ENST00000956320

RefSeq mRNA: 1 — MANE Select: NM_001105558 NM_001105558

CCDS: CCDS43660

Canonical transcript exons

ENST00000397541 — 12 exons

Exon	Start	End
ENSE00002430193	141725026	141725196
ENSE00002435326	141720935	141721056
ENSE00002447201	141714209	141714405
ENSE00002452229	141723941	141724048
ENSE00002462398	141724190	141724275
ENSE00002466375	141719072	141719244
ENSE00002467011	141727304	141727446
ENSE00002475135	141723134	141723280
ENSE00002482943	141708353	141709100
ENSE00002511151	141716222	141716267
ENSE00002519265	141729531	141729673
ENSE00002519956	141730295	141731271

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 91.16.

Top tissues by expression

122 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.15	gold quality
ganglionic eminence	UBERON:0004023	52.55	gold quality
endometrium	UBERON:0001295	51.25	gold quality
right uterine tube	UBERON:0001302	50.59	gold quality
calcaneal tendon	UBERON:0003701	48.90	gold quality
islet of Langerhans	UBERON:0000006	48.78	gold quality
mucosa of stomach	UBERON:0001199	48.75	gold quality
lower esophagus mucosa	UBERON:0035834	47.88	gold quality
endocervix	UBERON:0000458	47.45	gold quality
pancreas	UBERON:0001264	46.39	gold quality
bone marrow cell	CL:0002092	46.22	gold quality
muscle tissue	UBERON:0002385	45.88	silver quality
ventricular zone	UBERON:0003053	45.81	gold quality
body of pancreas	UBERON:0001150	45.40	gold quality
descending thoracic aorta	UBERON:0002345	44.94	gold quality
smooth muscle tissue	UBERON:0001135	44.91	gold quality
bone marrow	UBERON:0002371	44.91	gold quality
right ovary	UBERON:0002118	44.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	44.06	gold quality
cortex of kidney	UBERON:0001225	43.88	silver quality
sural nerve	UBERON:0015488	43.62	gold quality
fallopian tube	UBERON:0003889	43.53	gold quality
cortical plate	UBERON:0005343	43.34	gold quality
muscle of leg	UBERON:0001383	43.18	gold quality
prefrontal cortex	UBERON:0000451	43.11	gold quality
ovary	UBERON:0000992	42.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	42.87	gold quality
adult mammalian kidney	UBERON:0000082	42.79	gold quality
kidney	UBERON:0002113	42.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting WEE2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3177-5P	99.65	70.38	1174

Literature-anchored findings (GeneRIF, showing 9)

• homozygous mutations in WEE2 that are responsible for fertilization failure in humans, were identified. (PMID:29606300)
• WEE2-AS1 over-expressed in HCC and was positively correlated to hepatitis B virus (HBV) infection, hepatic vascular invasion, poor tumor differentiation and poor patient prognosis. WEE2-AS1 also accelerated the proliferation, migration, invasion and cell cycle progression of HCC cells. A preliminary HBx-WEE2-AS1- FERMT3 pathway which may serve as a therapeutic target for HBV-associated HCC. (PMID:30471857)
• These findings confirmed our previous research and expanded the mutational spectrum of WEE2, making it a potential genetic diagnostic marker for those suffering from human fertilization failure. (PMID:30628060)
• A high prevalence of WEE2 mutations was found in Chinese women experiencing fertilization failure or poor fertilization. (PMID:30827523)
• Novel variants found in WEE2, which is autosomal-recessive inherited, may be related to recurrent pronucleus formation failure and female infertility. (PMID:30827524)
• Novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female whose oocytes could not form pronucleus after intracytoplasmic sperm injection. Mutations in WEE2 gene affect the normal function of WEE2 proteins and cause fertilization failure. (PMID:31428887)
• Clinical exome sequencing identifies novel compound heterozygous mutations of the WEE2 gene in primary infertile women with fertilization failure. (PMID:33904356)
• Novel WEE2 compound heterozygous mutations identified in patients with fertilization failure or poor fertilization. (PMID:34476630)
• Novel WEE2 homozygous mutations c.1346C>T and c.949A>T identified in primary infertile women due to unexplained fertilization failure. (PMID:37772619)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	wee2	ENSDARG00000012718
mus_musculus	Wee2	ENSMUSG00000037159
rattus_norvegicus	Wee2	ENSRNOG00000026446
drosophila_melanogaster	Wee1	FBGN0011737

Paralogs (8): EIF2AK2 (ENSG00000055332), EIF2AK1 (ENSG00000086232), STK35 (ENSG00000125834), PKMYT1 (ENSG00000127564), EIF2AK4 (ENSG00000128829), WEE1 (ENSG00000166483), EIF2AK3 (ENSG00000172071), PDIK1L (ENSG00000175087)

Protein

Protein identifiers

Wee1-like protein kinase 2 — P0C1S8 (reviewed: P0C1S8)

Alternative names: Wee1-like protein kinase 1B, Wee1B kinase

All UniProt accessions (2): P0C1S8, H7C5P0

UniProt curated annotations — full annotation on UniProt →

Function. Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits CDK1/CDC2 and acts as a key regulator of meiosis during both prophase I and metaphase II. Required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, by phosphorylating CDK1 at ‘Tyr-15’, leading to inhibit CDK1 activity and prevent meiotic reentry. Also required for metaphase II exit during egg activation by phosphorylating CDK1 at ‘Tyr-15’, to ensure exit from meiosis in oocytes and promote pronuclear formation.

Subcellular location. Nucleus.

Tissue specificity. Expressed in oocytes (at protein level). May also be expressed in testis.

Post-translational modifications. Phosphorylated on serine residues. Phosphorylation leads to increase its activity.

Disease relevance. Oocyte/zygote/embryo maturation arrest 5 (OZEMA5) [MIM:617996] An autosomal recessive infertility disorder characterized by oocyte inability to exit metaphase II, resulting in fertilization failure. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.

RefSeq proteins (1): NP_001099028* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017164	Wee1-like_protein_kinase	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050339	CC_SR_Kinase	Family

Pfam: PF00069

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (48 total): helix 10, strand 10, sequence variant 6, compositionally biased region 4, binding site 4, turn 3, region of interest 2, sequence conflict 2, short sequence motif 2, chain 1, domain 1, active site 1, modified residue 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5VDK	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C1S8-F1	67.50	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 339 (proton acceptor)

Ligand- & substrate-binding residues (4): 218–226; 241; 344; 380

Post-translational modifications (1): 76

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_CELL_MATURATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_OOGENESIS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_ORGANELLE_FISSION, GOBP_POSITIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, GOBP_CELL_MATURATION, GOBP_NUCLEUS_ORGANIZATION

GO Biological Process (9): mitotic cell cycle (GO:0000278), female meiotic nuclear division (GO:0007143), female pronucleus assembly (GO:0035038), positive regulation of phosphorylation (GO:0042327), regulation of meiosis I (GO:0060631), regulation of fertilization (GO:0080154), negative regulation of oocyte maturation (GO:1900194), protein phosphorylation (GO:0006468), meiotic cell cycle (GO:0051321)

GO Molecular Function (9): magnesium ion binding (GO:0000287), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell cycle	2
meiotic nuclear division	2
phosphorylation	2
mitotic nuclear division	1
female gamete generation	1
meiotic cell cycle	1
nucleus organization	1
single fertilization	1
organelle assembly	1
regulation of phosphorylation	1
positive regulation of phosphate metabolic process	1
meiosis I	1
regulation of meiotic nuclear division	1
fertilization	1
regulation of reproductive process	1
oocyte maturation	1
regulation of oocyte maturation	1
negative regulation of cell maturation	1
negative regulation of reproductive process	1
protein modification process	1
sexual reproduction	1
reproductive process	1
metal ion binding	1
protein kinase activity	1
protein tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WEE2	PATL2	C9JE40	711
WEE2	TLE6	Q9H808	643
WEE2	TUBB8	Q3ZCM7	607
WEE2	CDC25B	P30305	601
WEE2	FBXO43	Q4G163	569
WEE2	BTG4	Q9NY30	538
WEE2	ZP3	P21754	500
WEE2	YWHAH	Q04917	497
WEE2	CCNB1	P14635	475
WEE2	BTRC	Q9Y297	452
WEE2	PLCZ1	Q86YW0	447
WEE2	ZP2	Q05996	444
WEE2	CDC25A	P30304	439
WEE2	CPEB1	Q9BZB8	423
WEE2	ATR	Q13535	421

IntAct

0 interactions, top by confidence:

BioGRID (2): WEE2 (Affinity Capture-MS), WEE2 (Dosage Lethality)

ESM2 similar proteins: A0JPN4, A4PES0, A4QNA8, D2HHP1, D4A7V9, E1BTE1, E2RSS3, O02776, O57473, O88622, O88866, P0C1S8, P47810, P47817, P54350, P57058, Q08D35, Q1LX29, Q1LX51, Q20443, Q2KIP2, Q63185, Q63802, Q66JT0, Q68UT7, Q6DFE0, Q6IRU7, Q6NVF4, Q6P1H6, Q6P1W0, Q6Z829, Q86W56, Q8AYG3, Q8AYK6, Q8BGE5, Q8BMI4, Q8C0Q4, Q8CFA1, Q8L4H0, Q8NG66

Diamond homologs: A4K2Q5, A4K2S1, A4PES0, A4QNA8, A5D791, D2HHP1, E1BTE1, E2RSS3, F4I1N8, O02827, O13148, O13889, O18209, O22042, O57473, O80397, P07527, P0C1S8, P11799, P15442, P27636, P29294, P30291, P32581, P33279, P47810, P47817, P54350, P54737, Q15746, Q1LX51, Q28824, Q4R8E0, Q54E34, Q54F40, Q54JQ1, Q54RP7, Q54ZN3, Q558U1, Q55F45

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WEE2	“down-regulates activity”	CDK1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

113 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	73
Likely benign	14
Benign	2

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
2163249	NM_001105558.1(WEE2):c.862C>T (p.Gln288Ter)	Pathogenic
4796631	NM_001105558.1(WEE2):c.1007_1008dup (p.His337fs)	Pathogenic
545469	NM_001105558.1(WEE2):c.700G>C (p.Asp234His)	Pathogenic
545470	NM_001105558.1(WEE2):c.1477dup (p.Thr493fs)	Pathogenic
977295	NM_001105558.1(WEE2):c.1228C>T (p.Arg410Trp)	Pathogenic
977296	NM_001105558.1(WEE2):c.1221G>A (p.Glu407=)	Pathogenic
977297	NM_001105558.1(WEE2):c.598C>T (p.Arg200Ter)	Pathogenic
545471	NM_001105558.1(WEE2):c.224_227del (p.Glu75fs)	Likely pathogenic

SpliceAI

1456 predictions. Top by Δscore:

Variant	Effect	Δscore
7:141709101:G:GG	donor_gain	1.0000
7:141714401:GATCT:G	donor_gain	1.0000
7:141714406:G:GG	donor_gain	1.0000
7:141716219:A:AG	acceptor_gain	1.0000
7:141716220:A:G	acceptor_gain	1.0000
7:141716221:GT:G	acceptor_gain	1.0000
7:141719070:A:AG	acceptor_gain	1.0000
7:141719071:G:GG	acceptor_gain	1.0000
7:141719071:GAGAT:G	acceptor_gain	1.0000
7:141719240:AATGA:A	donor_gain	1.0000
7:141719241:ATGA:A	donor_gain	1.0000
7:141719242:TGA:T	donor_gain	1.0000
7:141719242:TGAGT:T	donor_loss	1.0000
7:141719243:GA:G	donor_gain	1.0000
7:141719243:GAG:G	donor_gain	1.0000
7:141719244:AG:A	donor_loss	1.0000
7:141719245:G:GG	donor_gain	1.0000
7:141719245:GTG:G	donor_loss	1.0000
7:141719246:T:G	donor_loss	1.0000
7:141719248:AGTAC:A	donor_loss	1.0000
7:141720925:T:A	acceptor_gain	1.0000
7:141720930:CATA:C	acceptor_loss	1.0000
7:141720931:ATAG:A	acceptor_gain	1.0000
7:141720932:TAGG:T	acceptor_loss	1.0000
7:141720933:A:AG	acceptor_gain	1.0000
7:141720933:AG:A	acceptor_gain	1.0000
7:141720934:G:GA	acceptor_gain	1.0000
7:141720934:GG:G	acceptor_gain	1.0000
7:141720934:GGA:G	acceptor_gain	1.0000
7:141720934:GGAA:G	acceptor_gain	1.0000

AlphaMissense

3727 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:141719120:T:C	F212L	0.997
7:141719122:C:A	F212L	0.997
7:141719122:C:G	F212L	0.997
7:141721011:T:A	W279R	0.997
7:141721011:T:C	W279R	0.997
7:141719121:T:C	F212S	0.996
7:141721013:G:C	W279C	0.996
7:141721013:G:T	W279C	0.996
7:141719209:G:C	K241N	0.995
7:141719209:G:T	K241N	0.995
7:141723233:T:C	L327P	0.994
7:141724044:A:C	K377N	0.994
7:141724044:A:T	K377N	0.994
7:141727333:A:C	R474S	0.994
7:141727333:A:T	R474S	0.994
7:141724249:T:C	F399L	0.993
7:141724251:C:A	F399L	0.993
7:141724251:C:G	F399L	0.993
7:141725056:T:C	F418L	0.993
7:141725058:T:A	F418L	0.993
7:141725058:T:G	F418L	0.993
7:141719202:C:A	A239E	0.992
7:141723947:T:A	I345K	0.992
7:141727332:G:C	R474T	0.991
7:141719173:C:G	C229W	0.990
7:141719198:T:G	Y238D	0.990
7:141723269:A:T	D339V	0.990
7:141723270:C:A	D339E	0.990
7:141723270:C:G	D339E	0.990
7:141724039:T:G	Y376D	0.990

dbSNP variants (sampled 300 via entrez): RS1000102425 (7:141712348 T>C), RS1000174584 (7:141710889 G>A), RS1000413507 (7:141712066 G>A), RS1000602434 (7:141719624 T>C), RS1000740972 (7:141711858 G>C), RS1000911582 (7:141728056 TCCGGATGTGCTGACC>T), RS1001142813 (7:141726340 G>A), RS1001155245 (7:141712178 C>G), RS1001337771 (7:141725406 C>A), RS1001381012 (7:141718276 A>G), RS1001492527 (7:141725288 T>C), RS1001793933 (7:141731297 T>A,C), RS1001796426 (7:141720441 G>A,T), RS1001915483 (7:141712355 C>T), RS1002257680 (7:141726233 C>A,T)

Disease associations

OMIM: gene MIM:614084 | disease phenotypes: MIM:617996

GenCC curated gene-disease

Disease	Classification	Inheritance
oocyte maturation defect 5	Definitive	Autosomal recessive

Mondo (1): oocyte maturation defect 5 (MONDO:0020837)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000147	Polycystic ovaries
HP:0008222	Female infertility
HP:0008669	Abnormal spermatogenesis
HP:0011462	Young adult onset
HP:0020155	Abnormal oocyte morphology
HP:0031515	Abnormal meiosis
HP:0031516	Metaphase I oocyte maturation arrest
HP:0034719	Lack of oocyte pronucleus formation

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001961_2	Anorexia nervosa	2.000000e-07
GCST008017_2	Bitter taste perception (6-n-propylthiouracil) in obesity with metabolic syndrome	4.000000e-07
GCST008019_3	Bitter taste perception (phenylthiocarbamide) in obesity with metabolic syndrome	5.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5095 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 40,141 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL180022	NERATINIB	4	9,404
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL5416410	DASATINIB	4	655
CHEMBL603469	LESTAURTINIB	3
CHEMBL1976040	ADAVOSERTIB	2	1,738
CHEMBL475251	R-406	2	762
CHEMBL564829	MILCICLIB	2	821
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1908397	KW-2449	1	622
CHEMBL4289017	PF-03814735	1	537
CHEMBL49120	PD-0166285	1	455

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — WEE family

ChEMBL bioactivities

21 potent at pChembl≥5 of 21 total, top 21 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.41	Kd	3.9	nM	ADAVOSERTIB
8.33	Kd	4.7	nM	CHEMBL4067978
8.30	Kd	5	nM	PD-0166285
7.58	Kd	26.6	nM	MILCICLIB
7.57	Kd	27	nM	ADAVOSERTIB
7.24	Kd	57	nM	CHEMBL386051
7.03	Kd	94	nM	BOSUTINIB
6.97	Kd	106	nM	BOSUTINIB
6.89	Kd	128	nM	PF-03814735
6.70	Kd	200	nM	DASATINIB
6.32	Kd	481	nM	DASATINIB
6.30	Kd	498	nM	PELITINIB
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
5.89	Kd	1300	nM	NERATINIB
5.38	Kd	4200	nM	TOZASERTIB
5.33	Kd	4700	nM	KW-2449
5.22	Kd	6000	nM	FEDRATINIB
5.10	Kd	7900	nM	LESTAURTINIB
5.03	Kd	9400	nM	R-406

PubChem BioAssay actives

18 with measured affinity, of 158 total; 15 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	1450930: Binding affinity to recombinant human full-length N-terminal His8-tagged Wee2 (1 to 567 residues) expressed in human Expi293F cells assessed as dessociation constant by quantitative real-time PCR method	kd	0.0039	uM
4-(3,5-dichloro-4-methoxyanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile	1450946: Binding affinity to recombinant human N-terminal His6-tagged Wee2 kinase domain (202 to 492 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetry	kd	0.0047	uM
6-(2,6-dichlorophenyl)-2-[4-[2-(diethylamino)ethoxy]anilino]-8-methylpyrido[2,3-d]pyrimidin-7-one	1450946: Binding affinity to recombinant human N-terminal His6-tagged Wee2 kinase domain (202 to 492 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetry	kd	0.0050	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1450946: Binding affinity to recombinant human N-terminal His6-tagged Wee2 kinase domain (202 to 492 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetry	kd	0.0266	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624746: Binding constant for WEE2 kinase domain	kd	0.0570	uM
Bosutinib	624746: Binding constant for WEE2 kinase domain	kd	0.0940	uM
N-[2-[(1S,8R)-4-[[4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-11-yl]-2-oxoethyl]acetamide	1450946: Binding affinity to recombinant human N-terminal His6-tagged Wee2 kinase domain (202 to 492 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetry	kd	0.1280	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	624746: Binding constant for WEE2 kinase domain	kd	0.2000	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	1450946: Binding affinity to recombinant human N-terminal His6-tagged Wee2 kinase domain (202 to 492 residues) expressed in Escherichia coli BL21 (DE3) by isothermal titration calorimetry	kd	0.4980	uM
Neratinib	624746: Binding constant for WEE2 kinase domain	kd	1.3000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	624746: Binding constant for WEE2 kinase domain	kd	4.2000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624746: Binding constant for WEE2 kinase domain	kd	4.7000	uM
Fedratinib	624746: Binding constant for WEE2 kinase domain	kd	6.0000	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	624746: Binding constant for WEE2 kinase domain	kd	7.9000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624746: Binding constant for WEE2 kinase domain	kd	9.4000	uM

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1

ChEMBL screening assays

92 unique, capped per target: 92 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1059399	Binding	Inhibition of WEE2 assessed as enzyme activity at 1 uM relative to untreated control	Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and orally bioavailable aminoisoquinoline. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.